Summary

Plants synthesize an abundance of metabolites that can be exploited for pharmacological purposes (1). The pool of plant metabolites that can be considered medicinally important is greatly expanded when considering that many plant natural products can be used as a scaffold for derivatization, with the resulting unnatural analogs often having either improved or novel medicinal activity. Typically, unnatural analogs are made semi-synthetically by chemically modifying natural biosynthetic intermediates. However, on page 1224 of this issue, Lau and Sattely (2) report the discovery of a set of biosynthetic enzymes in mayapple (Podophyllum) plants that can produce a compound that is a direct precursor to etoposide, an “unnatural” anticancer agent. Moreover, Lau and Sattely show that the genes encoding these enzymes can be expressed in a different plant species to produce this etoposide precursor. The study clearly demonstrates the power of metabolic pathway discovery and genetic engineering to make not only naturally occurring compounds, but also natural product analogs with enhanced pharmacological value.